‘A lot of unknowns’: Much remains a mystery regarding sarcoidosis etiology, management

ORLANDO, Fla. — Despite a constellation of available data points regarding prognosis and impacted organs, researchers have so far been unable to connect the dots and form a better understanding of sarcoidosis, according to a presenter here.

“Sarcoidosis is a disease of unknown etiology,” Kalie VonFeldt, MS, PA-C, a physician’s assistant at National Jewish Health, in Denver, told attendees at the 2024 Rheumatology Nurses Society annual conference. “It is very similar to granulomatous lung diseases where we know the etiology.”

Because of that, VonFeldt described sarcoidosis as a diagnosis of exclusion. It is a multi-organ disease that is characterized by non-necrotizing granulomatous inflammation, and impacts people of most races and ethnicities relatively equally.

“Interestingly, women develop the disease later on,” VonFeldt said, noting that it tends to develop in men aged 30 to 40 years, and in women aged 40 to 60 years.

Some of the manifestations include brain complications, lymph node involvement, granulomatous scar tissue in the lungs, enlarged liver, erythema nodosum, enlarged spleen, heart involvement, skin lesions, eye problems and joint problems. Sarcoidosis may be acute or non-acute.

The acute form has a “good prognosis,” according to VonFeldt. However, just half of patients with the non-acute form make a full recovery, while approximately one-third develop a chronic course.

“This is not a disease that patients die from, but if they do die, the most common cause is respiratory failure,” she said.

Despite this information, providers still face significant challenges with sarcoidosis.

“There are a lot of unknowns,” VonFeldt said. “The disease course is so heterogeneous that it is really hard to figure it out.”

Consequently, guidelines and evidence for sarcoidosis are “really weak,” she added.

“We rely on each other in an expert-opinion way,” said VonFeldt.

That said, lung involvement is “pretty much a given” for most patients with sarcoidosis, according to VonFeldt. As a result, the workup often includes a pulmonary function test and a high-resolution CT of the chest. In addition, chest X-rays should be assessed using the Scadding Stage scale, with zero being a normal chest radiograph and a five being end-stage lung disease.

“Even though we do not think it progresses along that linear band, stage four is most severe and will not go away,” VonFeldt said. “You cannot reverse fibrosis. We can get them feeling better and we can get them off medication but they will never have normal lung function most likely.”

For patients with suspected sarcoidosis and cardiac involvement, an EKG is the most commonly used screening tool, along with an echocardiogram or a Holter monitor.

For rheumatology providers managing sarcoidosis, VonFeldt stressed that diffuse arthralgias are almost always present in patients with Lofgren’s syndrome.

“Most of my patients say their joints hurt,” she said. “However, we do not assume their arthritis is related to their sarcoidosis unless the rheumatologist tells us so.”

Sarcoidosis may also have neurological manifestations. Workup for these patients includes a brian MRI or a lumbar puncture.

“Brain MRI needs to be with and without contrast,” VonFeldt said.

Treatment for most patients with sarcoidosis begins with steroids. Of course, caution is required.

“If we know we are going to use prolonged steroids, we start an additional therapy at the same time,” VonFeldt said.

Methotrexate is the most common agent used in patients with lung, cardiac and neurological involvement, according to VonFeldt.

“Inhalers also really help patients with pulmonary involvement,” she added.

For patients with vitamin D and calcium abnormalities, steroids and hydroxychloroquine are the most commonly used first-line agents, followed by methotrexate, azathioprine or mycophenolate.

Meanhile, VonFeldt counseled caution regarding supplements.

“We have to be careful with vitamin D and calcium supplementation in patients with sarcoidosis due to kidney stones,” she said.

There remains no cure for sarcoidosis. Instead, providers should focus on controlling the disease and their patients symptoms as best they can, according to VonFeldt.

“The goal of treatment is always to make people feel better,” she said. “We want to control disease to avoid organ impairment. We really just want to improve their quality of life.”

That said, VonFeldt was adamant that providers should do everything they can to ensure the correct diagnosis.

“If we are committing them to treatment, we want to make sure we are treating the right thing,” she said.